nsun-1
C. elegans
26S rRNA (cytosine-C(5))-methyltransferase nsun-1
What the model saw
Gene: nsun-1 Organism: Caenorhabditis elegans Known functions: 26S rRNA (cytosine-C(5))-methyltransferase nsun-1. RNA binding. RNA methyltransferase activity. S-adenosylmethionine-dependent methyltransferase activity. methyltransferase activity. rRNA (cytosine-C5-)-methyltransferase activity.
View unredacted entry
26S rRNA (cytosine-C(5))-methyltransferase nsun-1. RNA binding. RNA methyltransferase activity. S-adenosylmethionine-dependent methyltransferase activity. methyltransferase activity. rRNA (cytosine-C5-)-methyltransferase activity.
Solver output
nsun-1 encodes a SAM-dependent RNA methyltransferase that installs C5-methylcytosine (m5C) modifications on 26S rRNA. Ribosomal RNA methylation by NSUN-family enzymes is critical for proper ribosome biogenesis, structural integrity, and translational fidelity. Accurate and efficient translation is a key determinant of proteostasis; defects in rRNA modification lead to aberrant ribosome assembly, reduced translational accuracy, and accumulation of misfolded proteins. In C. elegans, ribosome function and translational fidelity are tightly linked to longevity pathways, and proper rRNA modification supports the proteostasis network. Loss of nsun-1 function would be expected to impair ribosome quality and translational accuracy, thereby compromising proteostasis and reducing lifespan, making the normal function of nsun-1 pro-longevity.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model predicted pro_longevity but the ground truth is anti_longevity. The model reasoned that nsun-1 supports ribosome integrity and proteostasis, so its normal function should be pro-longevity. However, the ground truth indicates nsun-1 is anti_longevity, meaning its loss (or reduction) extends lifespan. This is consistent with findings in C. elegans where reduced translation/ribosome activity (e.g., through reduced ribosomal protein expression or rRNA modification) often extends lifespan - a well-known phenomenon in aging biology. The model's reasoning was plausible on the surface but missed the key insight that in C. elegans, reduced translational activity is frequently lifespan-extending, not lifespan-shortening. The model's mechanistic framing (proteostasis) was also incorrect in direction - reduced translation can actually improve proteostasis by reducing the load of misfolded proteins. The model had moderate confidence (0.62) but was wrong on both the answer and the mechanistic direction.
Raw API responses
solver
{
"reasoning": "nsun-1 encodes a SAM-dependent RNA methyltransferase that installs C5-methylcytosine (m5C) modifications on 26S rRNA. Ribosomal RNA methylation by NSUN-family enzymes is critical for proper ribosome biogenesis, structural integrity, and translational fidelity. Accurate and efficient translation is a key determinant of proteostasis; defects in rRNA modification lead to aberrant ribosome assembly, reduced translational accuracy, and accumulation of misfolded proteins. In C. elegans, ribosome function and translational fidelity are tightly linked to longevity pathways, and proper rRNA modification supports the proteostasis network. Loss of nsun-1 function would be expected to impair ribosome quality and translational accuracy, thereby compromising proteostasis and reducing lifespan, making the normal function of nsun-1 pro-longevity.",
"confidence": 0.62,
"key_pathways": [
"rRNA modification and ribosome biogenesis",
"translational fidelity and proteostasis",
"S-adenosylmethionine-dependent methylation"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model reasoned that nsun-1 supports ribosome integrity and proteostasis, so its normal function should be pro-longevity. However, the ground truth indicates nsun-1 is anti_longevity, meaning its loss (or reduction) extends lifespan. This is consistent with findings in C. elegans where reduced translation/ribosome activity (e.g., through reduced ribosomal protein expression or rRNA modification) often extends lifespan - a well-known phenomenon in aging biology. The model's reasoning was plausible on the surface but missed the key insight that in C. elegans, reduced translational activity is frequently lifespan-extending, not lifespan-shortening. The model's mechanistic framing (proteostasis) was also incorrect in direction - reduced translation can actually improve proteostasis by reducing the load of misfolded proteins. The model had moderate confidence (0.62) but was wrong on both the answer and the mechanistic direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}